| First Author | Haines BB | Year | 2006 |
| Journal | Cancer Cell | Volume | 9 |
| Issue | 2 | Pages | 109-20 |
| PubMed ID | 16473278 | Mgi Jnum | J:106246 |
| Mgi Id | MGI:3617930 | Doi | 10.1016/j.ccr.2006.01.004 |
| Citation | Haines BB, et al. (2006) Block of T cell development in P53-deficient mice accelerates development of lymphomas with characteristic RAG-dependent cytogenetic alterations. Cancer Cell 9(2):109-20 |
| abstractText | Mice deficient in the DNA damage sensor P53 display normal T cell development but eventually succumb to thymic lymphomas. Here, we show that inactivation of the TCR beta gene enhancer (E beta) results in a block of T cell development at stages where recombination-activating genes (RAG) are expressed. Introduction of the E beta mutation into p53-/- mice dramatically accelerates the onset of lethal thymic lymphomas that harbor RAG-dependent aberrant rearrangements, chromosome 14 and 12 translocations, and amplification of the chromosomal region 9A1-A5.3. Phenotypic and genetic analyses suggest that lymphomas emerge through a normal thymocyte development pathway. These findings provide genetic evidence that block of lymphocyte development at stages with RAG endonuclease activity can provoke lymphomagenesis on a background with deficient DNA damage responses. |
